1. End Stage Renal Disease
A healthy kidney removes toxic wastes and excess water from the blood. In End Stage Renal Disease ("ESRD"), or chronic kidney failure, the kidneys progressively stop performing these essential functions over a long period of time. When the kidneys fail, a patient dies within a short period of time unless that patient receives dialysis treatment for the rest of that patient's life or undergoes transplantation of a healthy, normal kidney. Because few kidneys are available for transplantation, the overwhelming majority of patients with ESRD receive dialysis treatment.
Hemodialysis therapy is an extracorporeal (i.e., outside the body) process which removes toxins and water from a patient's blood. A hemodialysis machine pumps blood from the patient, through a dialyzer, and then back to the patient. The dialyzer removes the toxins and water from the blood by a membrane diffusion principle. Typically, a patient with chronic kidney disease requires hemodialysis three times per week for 3-6 hours per session. Removing blood from the body requires a vascular access to the patient's blood system. This vascular access can be accomplished by surgically modifying the patient's own blood vessels or attaching an artificial device to the vessels. If the vascular access site is entirely beneath the skin, the skin and the vascular site must be punctured by a needle attached to blood tubing. This needle and tubing is typically called a "set".
This vascular access must remain patent (i.e., unblocked) and free from medical complications to enable dialysis to take place. It must allow blood to flow to the machine at a sufficiently high rate to permit dialysis to take place efficiently. And it should allow the patient to carry on a normal life.
2. Hemodialysis Vascular Access
A. Vascular Access--A Major Medical Need
Vascular access is widely called the "Achilles heel of dialysis" because high morbidity and mortality among dialysis patients is associated with complications of vascular access. Vascular access complications are believed to be the single greatest cause of morbidity and to account for approximately one-fourth of all admissions and hospitalization days in the hemodialysis population.
The financial impact to the health care system of these vascular access problems is enormous. By way of illustration, an analysis of the International Classification of Diseases (ICD-9) codes for the U.S. for 1993 showed over 91,000 procedures for the three codes dealing with (1) "Revise Renal Dialysis Shunt", (2) "Remove Renal Dialysis Shunt", and (3) "Complications of Renal Dialysis Device". More than 450,000 days of hospital stay days were involved for just these three codes alone. Clearly, the complications of the current methods of vascular access are costly, whether measured individually for a single event or aggregately for the whole patient population.
Thus, the need for improved vascular access is great.
B. Three Major Methods of Vascular Access
The major advances in vascular access for hemodialysis are listed below:
______________________________________ Year ______________________________________ Scribner shunt 1959 AV (arterio-venous) fistula 1966 Polytetrafluoroethylene (PTFE) graft 1977 Percutaneous catheter assembly 1983 implanted in jugular vein ______________________________________
1. The Scribner Shunt
The Scribner shunt was the breakthrough percutaneous device which enabled patients with chronic kidney disease to be treated with the primitive, already-existing hemodialysis machines. The Scribner shunt suffered from major infection and clotting problems and is no longer used.
2. The AV (Arterio-Venous) Fistula
The first of the three major methods of permanent vascular access currently in use is the native AV (arterio-venous) fistula. The AV fistula is a surgical construct connecting a patient's major artery to a major vein subcutaneously in the arm. With this new blood flow path, most blood will bypass the high flow resistance of the downstream capillary bed, thereby producing a dramatic increase in the blood flow rate through the fistula. Furthermore, although it is not medically feasible to repeatedly puncture an artery, formation of the fistula "arterializes" the vein. The arterialized vein can be punctured repeatedly, and the high blood flow permits high efficiency hemodialysis to occur. Two fistula needles, connected to blood tubing leading to and from the hemodialysis machine, are used to puncture the skin to gain access to the arterialized vein. Blood is withdrawn from the arterial side of the vein, passes through the machine, where it is cleansed, and returns to the venous side of the access.
3. Polytetrafluoroethylene (PTFE) Graft
The PTFE graft is an artificial, tubular, vascular graft made from polytetrafluoroethylene, a Teflon-type material. Implanted in a surgical procedure, the graft 5 (see FIG. 1) connects an artery 10 to a vein 15 in the arm, forming a bypass which can be punctured by fistula needle sets in the same way a normal AV fistula is accessed.
4. Percutaneous Catheter Assembly Implanted in Jugular Vein
The third method of vascular access for hemodialysis is a central venous percutaneous catheter assembly inserted into a major vein, such as the femoral, subclavian or jugular vein. For long term maintenance dialysis, the jugular vein is the preferred insertion site. These catheter assemblies are percutaneous, with one end external to the body and the other end dwelling in either the superior vena cava or the right atrium of the heart. The external portion of these catheter assemblies has connectors permitting attachment of blood sets leading to and from the hemodialysis machine.
FIGS. 2 and 3 show the traditional manner of positioning a central venous percutaneous catheter assembly 20 within the body. More particularly, percutaneous catheter assembly 20 generally comprises a catheter portion 21 comprising a catheter element 22, and a connector portion 24 comprising an extracorporeal connector element 25. The assembly's extracorporeal connector element 25 is disposed against the chest 30 of the patient, and the distal end 35 of catheter element 22 is passed into the patient's internal jugular vein 40 (FIG. 3) and then down into the patient's superior vena cava 45. More particularly, the distal end 35 of catheter element 22 is positioned within the patient's superior vena cava 45 such that the mouth 50 of suction line 55, and the mouth 60 of return line 65, are both located between the patient's right atrium 70 and the patient's left subclavia vein 75 and right subclavia vein 80. In this respect it is to be appreciated that, since mouth 60 of return line 65 is located distal to mouth 50 of suction line 55, mouth 60 of return line 65 will be located closer to right atrium 70 than is mouth 50 of suction line 55. Thus, mouth 60 of return line 65 is located downstream of mouth 50 of suction line 55. The percutaneous catheter assembly 20 is then left in this position relative to the body, waiting to be used during an active dialysis session.
When hemodialysis is to be performed on the patient, the assembly's extracorporeal connector element 25 is appropriately connected to a dialysis machine (not shown), i.e., suction line 55 is connected to the input port (i.e., the suction port) of the dialysis machine, and return line 65 is connected to the output port (i.e., the return port) of the dialysis machine. The dialysis machine is then activated (i.e., the dialysis machine's blood pump is turned on and the flow rate set), whereupon the dialysis machine will withdraw relatively "dirty" blood from the patient through suction line 55 and return relatively "clean" blood to the patient through return line 65. In this respect it is to be appreciated that, inasmuch as mouth 50 of suction line 55 is positioned upstream from mouth 60 of return line 65, the possibility of a hemodialysis "short circuit" (i.e., of suction line 55 collecting the relatively clean blood being returned to the patient's body by return line 65) will be reduced. In practice, it has generally been found desirable to separate the assembly's two mouths 50 and 60 by a distance of about 2 inches or so in order to avoid such undesired blood recirculation.
In some prior art applications, the distal end 35 of catheter element 22 may be positioned in the patient's right atrium 70 rather than in the patient's superior vena cava 45.
In one prior art construction, and looking now at FIG. 4, the construction of the distal end 35 of catheter element 22 is modified from that shown in FIG. 3. More particularly, in this alternative construction, the locations of the mouths 50 and 60 are reversed from that shown in FIG. 3, i.e., so that suction mouth 50 is disposed distal to return mouth 60. However, this design has not been favored, inasmuch as it presents the apparent risk of a hemodialysis "short circuit", i.e., where suction line 55 collects a substantial portion of the just-cleaned blood being returned to the patient's body by return line 65.
C. Benefits and Limitations of Each Method
FIG. 5 is a summary comparison of the benefits and limitations of each of the three currently-used major methods of hemodialysis vascular access.
1. Benefits and Limitations--the Native AV Fistula
The "gold standard" for vascular access is the native AV fistula. Because of its comparatively longer survival time and relatively lower level of major problems, it is the widely preferred choice of nephrologists. However, data from the 1997 U.S. Renal Data System Report indicates that only about 18% of all hemodialysis patients currently get a native AV fistula, while about 50% receive a PTFE graft and about 32% receive a percutaneous catheter assembly after two months of starting hemodialysis therapy.
The main reason that the AV fistula is not widely used is that the surgically-created AV fistula must "mature". Maturation occurs when high pressure and high blood flow from the connected artery expand the downstream system of veins to which it is surgically connected. Surgeons have found that successful AV fistula maturation is not possible in most patients because of the greatly increasing number of diabetic and older hemodialysis patients who have cardiovascular disease which prevents the maturation. Since surgeons have failed so often to achieve fistula maturation after performing the costly AV fistula surgery, they often no longer even try.
The other reason that AV fistulas are seldom used is that, even when fistula surgery is successful, maturation of the fistula generally takes approximately one to three months. Since about half of all prospective patients present with an immediate and urgent need to start hemodialysis, they cannot wait for AV fistula maturation to occur. They must undergo costly temporary procedures inserting percutaneous catheter assemblies to enable dialysis to take place.
2. Benefits and Limitations--the PTFE Graft
Given that AV fistulas are largely not possible, a PTFE vascular graft is implanted into the overwhelming majority of hemodialysis patients because, in spite of the relatively severe limitations to the PTFE graft, there is simply no better alternative.
The major disadvantages of the PTFE graft are stenosis (i.e., closing of the lumen) and thrombosis (i.e., clotting), both of which block the flow of blood. This dysfunction occurs in almost all graft patients several times in their lives and, because it interferes with life-sustaining dialysis, must be corrected quickly. Interventional procedures include angioplasty to open the stenosis and infusion of thrombolytic agents such as urokinase to dissolve the clots. Clinical studies report that the mean time of the operational use of the graft progressively decreases after each such corrective procedure until the operational time is so short that the surgeon decides to replace the graft. The survival time of the graft, including all repairs necessary to maintain its function, currently averages only about two years.
Medical interventions to maintain PTFE grafts and treatment for patient complications are expensive. Furthermore, declotting is required every 9 months or so on average. Also, because only three sites exist in each arm for placement of the graft, current practice is to perform additional screening procedures in an attempt to extend the survival time of the graft. These additional procedures add cost and inconvenience but have yet to significantly improve upon the mean time between interventional repair, although they may improve graft survival life.
PTFE grafts are structurally weakened, and the flow boundary is impaired, by the frequent (i.e., six times per week) puncturing with large gauge fistula needles. This degradation can lead to several complications and dysfunction, including post-dialysis bleeding, aneurysms and increased stenosis and thrombosis causing flow obstructions. Furthermore, a rough surface on the graft's exterior can become a place for bacteria to be protected from the body's defenses and antibiotic treatment. This further necessitates intervention and increases costs for access maintenance.
A PTFE graft (as well as an AV fistula) can also cause death in patients with heart problems. This is because the graft allows blood to bypass the lower circulation in the arm, which greatly reduces blood flow resistance in the arm as well as the whole body. The heart, which is a pump, recognizes lower system flow resistance and automatically adjusts to a higher cardiac output (i.e., a higher blood flow rate through the heart). Patients Who are older and with weak hearts may not adapt to this and can incur a cardiac arrest. Physicians considering this possibility currently screen out about 6% of all hemodialysis patients from acquiring a graft or fistula.
An additional disadvantage to PTFE grafts is that they take time to mature before they can be used. About 50% of patients present with a need for immediate hemodialysis and the surgeon must place a temporary access (i.e., a central venous percutaneous catheter assembly) for immediate use while the graft is maturing. This usually takes several weeks. The cost to place an additional vascular access for hemodialysis further consumes medical resources.
Another limitation of PTFE grafts is that the Teflon-type material does not seal as well as a native vein after removal of the fistula needle. Also, pressure in the graft is higher than venous pressure. This typically results in blood spurting out of the hole created by the needle puncture upon withdrawal of the needle. Achieving hemostasis requires that the puncture site be held with a finger or other means for a considerable period of time (usually 10 to 20 minutes) while maintaining pressure until the blood clots and bleeding stops.
3. Benefits and Limitations--Central Venous Percutaneous Catheter Assembly
The third method of permanent vascular access is a percutaneous central venous catheter assembly inserted through the skin into a major vein, with the distal tips of the catheter element advanced into the right atrium of the heart or the superior vena cava, a major vein leading into the right atrium. Percutaneous catheter assemblies have been used in hemodialysis since the early 1960's but were for many years considered "temporary" vascular access because of major infection and stenosis problems. Because they can be easily and quickly inserted, they were used only when emergency vascular access was needed to permit hemodialysis. For many years, potentially life-threatening infection complications were so great that the percutaneous catheter assemblies were withdrawn after each dialysis session and re-inserted before the next session so as to minimize the risk of infection.
Two important developments were made in the 1980's that have led some nephrologists to consider percutaneous catheter assemblies as "permanent" vascular access. The most important of these developments was a 1983 paper reporting the insertion of percutaneous catheter assemblies into the jugular vein rather than the subclavian vein. Jugular vein insertion essentially eliminated the problem of subclavian vein stenosis associated with up to 50% of subclavian vein catheter insertions. Subclavian vein stenosis not only blocks blood flow, making it impossible to conduct hemodialysis, but also, catastrophically, can destroy all potential vascular access sites in one or both arms. Given the short survival time for all vascular access sites, preservation of vascular access sites is a major imperative of artificial kidney treatment.
The second major development was the attachment of a dacron "cuff" to the assembly's catheter element, near the proximal end, under the skin, about an inch from the incision site where the assembly exits the body. This cuff permits tissue in-growth to occur which fastens the catheter element to the tissue, thereby reducing movement of the percutaneous catheter assembly at the incision site as well as in the blood vessel. In addition, such tissue in-growth is believed by many to retard bacterial travel along the outer surface of the percutaneous catheter assembly, although it does not prevent it entirely. While numerous reports suggest that the cuff has reduced the infection rate, infections remain a major problem with the use of cuffed percutaneous catheter assemblies.
Because of these developments, a series of papers published in the 1990's reported positively on the long term survival of percutaneous catheter assemblies, thereby permitting their use in "permanent" vascular access. It is anticipated, however, that PTFE grafts will continue to be preferred to percutaneous catheter assemblies because PTFE grafts permit longer use without intervention (see FIG. 5).
The principal factor limiting percutaneous catheter assembly survival, and time without incidents requiring medical intervention, is infection, which continues to occur at a high rate. Clinical experience indicates that about 82% of all percutaneous catheter assembly failures and complications are attributable to infection.
To make percutaneous catheter assemblies a widely accepted form of permanent vascular access, one must resolve infection complications. However, as long as the percutaneous catheter assembly breaks through the skin, which is the body's barrier to infection, the pathway for bacteria from outside the body to the subcutaneous tissue exists. It should be noted that the PTFE graft, which is entirely subcutaneous, has a much lower rate of infection than the percutaneous catheter assembly. With a PTFE graft, the skin and the graft are in contact only with sterile fistula needles during the dialysis session.
Another limitation to percutaneous catheter assemblies compared to PTFE grafts is that, historically, permissible blood flow rates are much lower with percutaneous catheter assemblies because the pressure drop through the percutaneous catheter assembly is higher than through a PTFE graft. As a result, it has been difficult to conduct the high efficiency (i.e., the short time) dialysis protocols used in for-profit dialysis centers with percutaneous catheter assembly access.
Percutaneous catheter assemblies also have problems with flow obstructions. More particularly, when a percutaneous catheter is left in the body for a significant period of time, fibrin sheaths can form about the distal end of the catheter element, and these fibrin sheaths can obstruct the flow of blood into the mouth of the suction line. In addition, blood clots can also obstruct the flow of blood into the mouth of the catheter assembly's suction line. Furthermore, if the distal tip of the catheter element engages the side wall of the host blood vessel, the catheter element can irritate the side wall of that blood vessel, causing tissue to grow about the distal tip of the catheter element. This tissue can also obstruct the flow of blood into the mouth of the catheter assembly's suction line.
Also, at high dialysis flow rates, suction line 55 of catheter element 22 can sometimes draw the side wall 85 (FIG. 6) of superior vena cava 45 inward, toward mouth 50 of suction line 55, due to its aggressive suction action. When this occurs, side wall 85 may interfere with the flow of blood into mouth 50 of suction line 55. In addition, this inward movement of side wall 85 also acts to narrow the internal diameter of superior vena cava 45, thereby reducing the rate at which blood may be withdrawn from, or returned to, that host blood vessel. Both of these effects can reduce the throughput of the dialysis machine, thereby increasing the patient's dialysis time and reducing the total number of patients who may be treated with that particular dialysis machine. On the other hand, if the level of suction is lowered so as to reduce the possibility of drawing side wall 85 into mouth 50 of suction line 55, then the overall flow of blood through the percutaneous catheter assembly will also be reduced, thereby again decreasing the total throughput of the dialysis machine.
Also, patient acceptance of percutaneous catheter assemblies has always been low due to self-image concerns and limitations on life style. The percutaneous catheter assembly exiting the body from the neck or chest is a visible reminder (both to the patient and others) of the patient's hemodialysis-machine-dependent illness. Patients also tend to dislike percutaneous catheter assemblies because bathing and other normal activities generally have to be restricted to protect the percutaneous catheter assembly.
In addition to the foregoing, it has also been found that air embolisms can be accidentally introduced into the patient when using percutaneous catheter assemblies.
Also, it has been found that the percutaneous catheter assembly's extracorporeal connector element can be damaged by undesired contact during the periods between dialysis sessions.
Percutaneous catheter assemblies do have certain inherent advantages, however. For one thing, they can be quickly, easily, and inexpensively inserted into the patient. In addition, there is no detrimental physical effect to the device from frequent use because, unlike PTFE grafts, it is not necessary to repeatedly puncture the device with large gauge fistula needles. Furthermore, there are few post-dialysis bleeding problems at the access site because the blood conduit is not punctured with fistula needles.
D. Subcutaneous Infusion Port Assemblies
Subcutaneous infusion port assemblies are currently in use in the field of oncology, to facilitate the repeated and regular delivery of chemotherapy agents to cancer patients. Such subcutaneous infusion port assemblies generally comprise a needle-receiving septum and a fluid line extending out of the needle-receiving septum. The subcutaneous infusion port assembly is surgically implanted in the patient's body on a semi-permanent basis, with the needle-receiving septum being disposed subcutaneously in the chest area of the patient, and with the fluid line leading from the needle-receiving septum into the vascular system of the patient. During a chemotherapy session, medical personnel pass a needle through the skin of the patient and into fluid engagement with the subcutaneous needle-receiving septum. This arrangement allows the desired chemotherapy agents to be delivered from a location outside the body into the subcutaneous needle-receiving septum, whereupon the chemotherapy agents can flow into the patient's vascular system so as to effect the desired treatment.
Only one known prior art attempt has been made to use chemotherapy infusion port assemblies in hemodialysis applications. This attempt was not satisfactory, for a variety of reasons.